Orthopoxvirus DNA in Eurasian Lynx, Sweden

Cowpox virus, which has been used to protect humans against smallpox but may cause severe disease in immunocompromised persons, has reemerged in humans, domestic cats, and other animal species in Europe. Orthopoxvirus (OPV) DNA was detected in tissues (lung, kidney, spleen) in 24 (9%) of 263 free-ranging Eurasian lynx (Lynx lynx) from Sweden. Thymidine kinase gene amplicon sequences (339 bp) from 21 lynx were all identical to those from cowpox virus isolated from a person in Norway and phylogenetically closer to monkeypox virus than to vaccinia virus and isolates from 2 persons with cowpox virus in Sweden. Prevalence was higher among animals from regions with dense, rather than rural, human populations. Lynx are probably exposed to OPV through predation on small mammal reservoir species. We conclude that OPV is widely distributed in Sweden and may represent a threat to humans. Further studies are needed to verify whether this lynx OPV is cowpox virus

Jämförelse av roller inom olika projekt: Traditionell projektledning och Scrum

Bakgrunden till denna studie är problemen som uppstår på grund av implementeringen av utvecklingsmetoden Scrum. Enligt Schwaber (2004) så försöker många företag att behålla sina projektledare även efter att ha implementerat Scrum. Därmed undersöker vi om de två nya rollerna som tillkommer med metoden, produktägare och scrummaster, ersätter den traditionella projektledaren och i så fall, på vilket sätt. Genom att göra en kvalitativ undersökning med sex intervjuer så har vi klarlagt deras uppgifter, krav och egenskaper. Detta sammanställer vi i tabell 5.2 där man tydligt ser att Scrumrollerna inte ersätter projektledaren till fullo samt att Scrum har vissa uppgifter som projektledaren inte har. Slutligen avslutar vi med en reviderad version av vårt ramverk

Quantum Acoustics with Surface Acoustic Waves

It has recently been demonstrated that surface acoustic waves (SAWs) can interact with superconducting qubits at the quantum level. SAW resonators in the GHz frequency range have also been found to have low loss at temperatures compatible with superconducting quantum circuits. These advances open up new possibilities to use the phonon degree of freedom to carry quantum information. In this paper, we give a description of the basic SAW components needed to develop quantum circuits, where propagating or localized SAW-phonons are used both to study basic physics and to manipulate quantum information. Using phonons instead of photons offers new possibilities which make these quantum acoustic circuits very interesting. We discuss general considerations for SAW experiments at the quantum level and describe experiments both with SAW resonators and with interaction between SAWs and a qubit. We also discuss several potential future developments.Comment: 14 pages, 12 figure

Actinomadura meyerae osteitis following wound contamination with hay in a woman in France: a case report

<p>Abstract</p> <p>Introduction</p> <p>Mycetoma is a chronic granulomatous infection caused by environmental fungi or bacteria. It affects dermal and subcutaneous tissues, with putative contiguous extension to muscles or bones. While common in tropical and subtropical areas, mycetoma is rare in Europe.</p> <p>Case presentation</p> <p>We describe a case of <it>Actinomadura meyerae </it>osteitis in a 49-year-old Caucasian woman who suffered a tibia open fracture contaminated with hay; to the best of our knowledge the first case of autochthonous <it>A. meyerae </it>infection reported in France. The bacterium was cultivated from a bone biopsy. Following surgical osteosynthesis and six months of treatment with cotrimoxazole, our patient made a full recovery.</p> <p>Conclusion</p> <p>Our case report suggests that <it>A. meyerae </it>is a potential agent of wound infection in farm workers in contact with hay.</p

LKB1 Destabilizes Microtubules in Myoblasts and Contributes to Myoblast Differentiation

Background: Skeletal muscle myoblast differentiation and fusion into multinucleate myotubes is associated with dramatic cytoskeletal changes. We find that microtubules in differentiated myotubes are highly stabilized, but premature microtubule stabilization blocks differentiation. Factors responsible for microtubule destabilization in myoblasts have not been identified. Findings: We find that a transient decrease in microtubule stabilization early during myoblast differentiation precedes the ultimate microtubule stabilization seen in differentiated myotubes. We report a role for the serine-threonine kinase LKB1 in both microtubule destabilization and myoblast differentiation. LKB1 overexpression reduced microtubule elongation in a Nocodazole washout assay, and LKB1 RNAi increased it, showing LKB1 destabilizes microtubule assembly in myoblasts. LKB1 levels and activity increased during myoblast differentiation, along with activation of the known LKB1 substrates AMPactivated protein kinase (AMPK) and microtubule affinity regulating kinases (MARKs). LKB1 overexpression accelerated differentiation, whereas RNAi impaired it. Conclusions: Reduced microtubule stability precedes myoblast differentiation and the associated ultimate microtubule stabilization seen in myotubes. LKB1 plays a positive role in microtubule destabilization in myoblasts and in myoblast differentiation. This work suggests a model by which LKB1-induced microtubule destabilization facilitates the cytoskeleta

LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in Hepatocytes.

Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation

Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

<p>Abstract</p> <p>Background</p> <p>Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid) injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal). These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability.</p> <p>Methods</p> <p>In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively) or placebo (NCT#00590577). Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS) score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity) using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE) rates and relative risks (RR) with 95% confidence intervals (CI) versus placebo were determined.</p> <p>Results</p> <p>Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS) mean PANSS total score at Day 8 (p = 0.037). After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo) and Day 36 (p < 0.001). Taken together with results in the 39 mg and 234 mg Day 8 arms, these findings suggest a trend towards a dose-dependent response. During Days 1 to 7, AEs reported in ≥2% of paliperidone palmitate subjects (234 mg) and a greater proportion of paliperidone palmitate than placebo subjects were: agitation (3.2% vs. 1.3%; RR 2.52 [95% CI 0.583, 10.904]), headache (4.0% vs. 3.8%; RR 1.06 [95% CI 0.433, 2.619]), and injection site pain (6.7% vs. 3.8%; RR 1.79 [95% CI 0.764, 4.208]). Days 8 to 36 AEs meeting the same criteria in the 156 mg Day 8 arm were: anxiety (3.1% vs. 2.5%; RR 1.24 [95% CI 0.340, 4.542]), psychotic disorder (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), dizziness (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), and injection site pain (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]). Corresponding Days 8 to 36 AEs in the 39 mg Day 8 group were: agitation (4.5% vs. 4.4%; RR 1.03 [95% CI 0.371, 2.874]), anxiety (3.9% vs. 2.5%; RR 1.55 [95% CI 0.446, 5.381]), and psychotic disorder (2.6% vs. 1.3%; RR 2.07 [95% CI 0.384, 11.110]) while in the 234 mg Day 8 group it was anxiety (3.1% vs. 2.5%, RR 1.25 [95% CI 0.342, 4.570]).</p> <p>Conclusions</p> <p>Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1) compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose-dependent response. No unexpected tolerability findings were noted in the first week or month after the initiation dosing.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT#00590577">NCT#00590577</a></p

Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea

Emerging clinical data indicate that transfusion-dependent patients with bone marrow-failure syndromes (BMFS) are at risk of the consequences of iron overload, including progressive damage to hepatic, endocrine, and cardiac organs. Despite the availability of deferoxamine (DFO) in Korea since 1998, data from patients with myelodysplastic syndromes, aplastic anemia, and other BMFS show significant iron overload and damage to the heart and liver. The recent introduction of deferasirox, a once-daily, oral iron chelator, may improve the availability of iron chelation therapy to iron-overloaded patients, and improve compliance in patients who may otherwise find adherence to the DFO regimen difficult

General Practitioners' opinions on their practice in mental health and their collaboration with mental health professionals

BACKGROUND: Common mental health problems are mainly treated in primary care settings and collaboration with mental health services is needed. Prior to re-organisation of the mental health care offer in a geographical area, a study was organized: 1) to evaluate GPs' opinions on their day-to-day practice with Patients with Mental Health Problems (PMHP) and on relationships with Mental Health Professionals (MHPro); 2) to identify factors associated with perceived need for collaboration with MHPro and with actual collaboration. METHODS: All GPs in the South Yvelines area in France (n = 492) were informed of the implementation of a local mental health program. GPs interested in taking part (n = 180) were invited to complete a satisfaction questionnaire on their practice in the field of Mental Health and to include prospectively all PMHP consultants over an 8-day period (n = 1519). For each PMHP, data was collected on demographic and clinical profile, and on needs (met v. unmet) for collaboration with MHPro. RESULTS: A majority of GPs rated PMHP as requiring more care (83.4%), more time (92.3%), more frequent consultations (64.0%) and as being more difficult to refer (87.7%) than other patients. A minority of GPs had a satisfactory relationship with private psychiatrists (49.5%), public psychiatrists (35%) and social workers (27.8%). 53.9% had a less satisfactory relationship with MHPro than with other physicians. Needs for collaboration with a MHPro were more often felt in caring for PMHP who were young, not in employment, with mental health problems lasting for more than one year, with a history of psychiatric hospitalization, and showing reluctance to talk of psychological problems and to consult a MHPro. Needs for collaboration were more often met among PMHP with past psychiatric consultation or hospitalization and when the patient was not reluctant to consult a MHPro. Where needs were not met, GP would opt for the classic procedure of mental health referral for only 31.3% of their PMHP. CONCLUSION: GPs need targeted collaboration with MHPro to support their management of PMHP, whom they are willing to care for without systematic referral to specialists as the major therapeutic option